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Metamolecule clusters support various unique types of artificial electromagnetism at optical frequencies. However, the technological challenges regarding the freeform fabrication of freestanding metamolecule clusters with programmed geometries and multiple compositions remain unresolved. Here, the freeform, freestanding raspberry-like metamolecule (RMM) fibers based on the directional guidance of a femtoliter meniscus are presented, resulting in the evaporative co-assembly of silica nanoparticles and gold nanoparticles with the aid of 3D nanoprinting. This method offers a facile and universal pathway to shape RMM fibers in 3D, enabling versatile manipulation of near- and far-field characteristics. In particular, the authors demonstrate the ability to decrease the scattering of the millimeter-scale RMM fiber in visible spectrum. In addition, the influence of electric and magnetic dipole modes on the directional scattering of RMM fibers is investigated. These experiments show that the magnetic response of an individual RMM can be controlled by adjusting the filling factor of gold nanoparticles. The authors anticipate that this method will allow for unrestricted design and realization of nanophotonic structures, surpassing the limitations of conventional fabrication processes.
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Nanoimprint lithography (NIL) has been utilized to address the manufacturing challenges of high cost and low throughput for optical metasurfaces. To overcome the limitations inherent in conventional imprint resins characterized by a low refractive index (n), high-n nanocomposites have been introduced to directly serve as meta-atoms. However, comprehensive research on these nanocomposites is notably lacking. In this study, we focus on the composition of high-n zirconium dioxide (ZrO2) nanoparticle (NP) concentration and solvents used to produce ultraviolet (UV) metaholograms and quantify the transfer fidelity by the measured conversion efficiency. The utilization of 80 wt% ZrO2 NPs in MIBK, MEK, and acetone results in conversion efficiencies of 62.3%, 51.4%, and 61.5%, respectively, at a wavelength of 325 nm. The analysis of the solvent composition and NP concentration can further enhance the manufacturing capabilities of high-n nanocomposites in NIL, enabling potential practical use of optical metasurfaces.
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Conventional photonic devices exhibit static optical properties that are design-dependent, including the material's refractive index and geometrical parameters. However, they still possess attractive optical responses for applications and are already exploited in devices across various fields. Hydrogel photonics has emerged as a promising solution in the field of active photonics by providing primarily deformable geometric parameters in response to external stimuli. Over the past few years, various studies have been undertaken to attain stimuli-responsive photonic devices with tunable optical properties. Herein, we focus on the recent advancements in hydrogel-based photonics and micro/nanofabrication techniques for hydrogels. In particular, fabrication techniques for hydrogel photonic devices are categorized into film growth, photolithography (PL), electron-beam lithography (EBL), and nanoimprint lithography (NIL). Furthermore, we provide insights into future directions and prospects for deformable hydrogel photonics, along with their potential practical applications.
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OBJECTIVES: Neuroendocrine tumors (NETs) are a heterogeneous group of tumors that arise at various sites throughout the body. The gastroenteropancreatic (GEP) tract is the most common site of NETs. We investigated the clinicopathologic features of patients with GEP-NETs and the utility of digital image analysis, which was compared to eyeball estimation, a conventional method used to determine the Ki-67 labeling index. METHODS: The clinicopathologic data of GEP-NET patients at Gangnam Severance Hospital from January 2008 to October 2019 were retrospectively analyzed. Each case was reclassified according to the 2019 World Health Organization classification system, to which the classification of grade 3 was added. Comparisons between eyeball estimation and the digital image analysis method for Ki-67 index assessment were performed by calculating Cohen's kappa (k) coefficient. RESULTS: In total, 345 patients with GEP-NETs were enrolled. The mean age was 49.3 (range 13-79) years, with more male (61.1%) than female patients. The primary tumor sites were the rectum (70.1%), pancreas (12.5%), stomach (6.7%), and duodenum (5.8%). Overall, 298 (86.4%), 35 (10.1%), 2 (0.6%), and 10 (2.9%) patients exhibited grade 1, 2, and 3 and neuroendocrine carcinoma, respectively. Statistical analysis revealed that age > 50 years, tumor size > 2 cm, and presence of lymphovascular invasion, nodal metastasis, and distant metastasis were significantly associated with short overall survival. Additionally, 283 patients underwent digital image analysis of the Ki-67 index, and substantial agreement was found between the two methods (κ value: 0.765). CONCLUSIONS: Eyeball estimation revealed non-inferior results compared with digital image analysis. Further research is needed to evaluate the possibility of using digital image analysis as an alternative analysis method.
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Tubulointerstitial fibrosis is characterized by accumulation of the extracellular matrix in the interstitium. Lysyl oxidase-like 2 (LOXL2), a member of the lysyl oxidase family, is known for promoting cancer metastasis, invasion and stromal fibrosis in various organs. Our previous study demonstrated expression of LOXL2 in kidney podocytes and tubular epithelial cells, and the association between elevated LOXL2 and tubulointerstitial fibrosis. The present study evaluated the effect of LOXL2 inhibition using an inhibitory monoclonal antibody (AB0023) on tubulointerstitial fibrosis in a folic acid-induced tubulointerstitial fibrosis mouse model. The association of LOXL2 with epithelial-mesenchymal transformation-related molecules was also evaluated in vitro using HK-2 cells. The present data demonstrated that AB0023 prevented the progression of tubulointerstitial fibrosis significantly, as determined by trichrome and picro-sirius red staining, as well as the total collagen assay. The mean expression of phosphorylated Smad2 and Smad4 was lower in the AB0023-treated group although it was not statistically significant. Following transforming growth factor-ß (TGF-ß) challenge, LOXL2-deficient HK-2 cells exhibited significantly lower expression of the mesenchymal markers vimentin and fibronectin than control HK-2 cells. In conclusion, LOXL2 inhibition ameliorates renal fibrosis through the TGF-ß/Smad signalling pathway.
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Artificial chiral structures have potential applications in the field of enantioselective signal sensing. Advanced nanofabrication methods enable a large diversity in geometric structures and broad selectivity of materials, which can be exploited to manufacture artificial three-dimensional chiral structures. Various chiroptical phenomena exploiting spin and orbital angular momentum at the nanoscale have been continuously exploited as a way to effectively detect enantiomers. This review introduces precisely controlled bottom-up and large-area top-down metamaterial fabrication methods to solve the limitations of high manufacturing cost and low production speed. Particle synthesis, self-assembly, glanced angled vapor deposition, and three-dimensional plasmonic nanostructure printing are introduced. Furthermore, emerging sensitive chiral sensing methods such as cavity-enhanced chirality, photothermal circular dichroism, and helical dichroism of single particles are discussed. The continuous progress of nanofabrication technology presents the strong potential for developing artificial chiral structures for applications in biomedical, pharmaceutical, nanophotonic systems.
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Metasurface-driven optical encryption devices have attracted much attention. Here, we propose a dual-band vectorial metahologram in the visible and ultraviolet (UV) regimes for optical encryption. Nine polarization-encoded vectorial holograms are observed under UV laser illumination, while another independent hologram appears under visible laser illumination. The proposed engineered silicon nitride, which is transparent in UV, is employed to demonstrate the UV hologram. Nine holographic images for different polarization states are encoded using a pixelated metasurface. The dual-band metahologram is experimentally implemented by stacking the individual metasurfaces that operate in the UV and visible. The visible hologram can be decrypted to provide the first key, a polarization state, which is used to decode the password hidden in the UV vectorial hologram through the use of an analyzer. Considering the property of UV to be invisible to the naked eye, the multiple polarization channels of the vectorial hologram, and the dual-band decoupling, the demonstrated dual-band vectorial hologram device could be applied in various high-security and anticounterfeiting applications.
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Interleukin-4 (IL-4) expression is implicated in the pathogenesis of nephrotic syndrome (NS). This study aimed to investigate the changes in the transcriptomes of human podocytes induced by IL-4 treatment and to analyze whether these changes could be affected by simultaneous steroid treatment. Three groups of human podocytes were treated with control, IL-4, and IL-4 plus dexamethasone (DEX), respectively. We performed whole-transcriptome sequencing to identify differentially expressed genes (DEGs) between the groups. We investigated relevant biological pathways using Gene Ontology (GO) enrichment analyses. We also attempted to compare and validate the DEGs with the genes listed in PodNet, a literature-based database on mouse podocyte genes. A total of 176 genes were differentially expressed among the three groups. GO analyses showed that pathways related to cytoskeleton organization and cell signaling were significantly enriched. Among them, 24 genes were listed in PodNet, and 12 of them were previously reported to be associated with IL-4-induced changes in human podocytes. Of the 12 genes, the expression levels of BMP4, RARB, and PLCE1 were reversed when podocytes were simultaneously treated with DEX. In conclusion, this study explored changes in the transcriptome profiles of human podocytes treated with IL-4. Few genes were reported in previous studies and were previously validated in experiments with human podocytes. We speculate that IL-4 may exert pathogenic effects on the transcriptome of human podocytes, and a few genes may be involved in the pathogenesis.
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The effects of MMHD [(S,E)-2-methyl-1-(2-methylthiazol-4-yl) hexa-1,5-dien-ol], a novel synthetic compound derived from epothilone, was investigated for its effects on the expression of proinflammatory mediators in lipopolysaccharide-stimulated BV-2 microglia. MMHD attenuated the expressions of inducible nitric oxide synthase and cyclooxygenase-2 mRNA and protein without affecting cell viability. Moreover, MMHD suppressed nuclear factor-kappaB (NF-kappaB) activation via the translocation of p65 into the nucleus. These results indicate that MMHD exerts anti-inflammatory properties by suppressing the transcription of proinflammatory cytokine genes through the NF-kappaB signaling pathway.
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Anti-Inflamatórios/farmacologia , Citocinas/efeitos dos fármacos , Microglia/efeitos dos fármacos , Tiazóis/farmacologia , Animais , Sobrevivência Celular/efeitos dos fármacos , Ciclo-Oxigenase 2/efeitos dos fármacos , Ciclo-Oxigenase 2/genética , Citocinas/metabolismo , Regulação da Expressão Gênica/efeitos dos fármacos , Mediadores da Inflamação/metabolismo , Lipopolissacarídeos/farmacologia , Camundongos , Microglia/metabolismo , NF-kappa B/metabolismo , Óxido Nítrico Sintase Tipo II/efeitos dos fármacos , Óxido Nítrico Sintase Tipo II/genética , Transporte Proteico/efeitos dos fármacos , RNA Mensageiro/efeitos dos fármacos , RNA Mensageiro/metabolismo , Fator de Transcrição RelA/metabolismoRESUMO
Tubulointerstitial fibrosis is a common end point of chronic kidney diseases, and preventing its progression is key to avoiding renal failure. Transforming growth factorß (TGFß) and associated molecules promote tubulointerstitial fibrosis; however, effective therapies targeting these molecules have yet to be developed. Lysyl oxidaselike 2 (LOXL2), which is involved in invasive growth and metastasis of malignant neoplasms, has recently been reported to serve a key role in hepatic and pulmonary fibrosis. However, little is currently known regarding LOXL2 expression in the kidney and its involvement in tubulointerstitial fibrosis. The present study evaluated LOXL2 expression in human and mouse kidney tissues, as well as in cultured renal cells. LOXL2 protein expression was detected in glomerular capillary loops and tubular epithelial cells in human and mouse kidneys. Glomerular LOXL2 was localized to the cytoplasm of podocytes, as determined by double immunofluorescence microscopy using a podocyte marker (synaptopodin). This result was supported by western blot analysis, which demonstrated that LOXL2 protein expression is present in cultured human podocytes and HK2 human proximal tubular cells. In addition, the mRNA and protein expression levels of LOXL2 were higher in a mouse model of tubulointerstitial fibrosis compared with in control mice. In addition, immunohistochemistry results demonstrated that LOXL2 is present in the fibrous interstitium and infiltrating mononuclear cells in a mouse model of tubulointerstitial fibrosis. The present study demonstrated that LOXL2 is expressed in compartments of renal tissue, where it appears to contribute to the progression of tubulointerstitial fibrosis.